This proposal is designed to development methods for isotopic measurement of axonal transport in living nerves in vivo and in vitro. In these studies two recently developed approaches will be used in conjunction: first, a cadmium telluride crystal microprobe, developed as a collaborative project with the Johns Hopkins Applied Physics Laboratory will be used to detect -emissions from peripheral nerve in vivo and in vitro. Second, a modification of the Fink-Gainer method will be developed to label transported proteins; our studies will use N-succinimidyl 3-(4-hydroxy,5-[125I]-iodophenyl) propionate (NS125IPP) to covalently link a gamma-emitting label to previously synthesized axonal proteins. Preliminary results indicate that these approaches allow labeling of transported proteins either by conventional application of NS125IPP near neuronal perikarya, or by local injection along the course of the nerve. Fast anterograde and retrograde transport, slo anterograde transport, and slow retrograde movement of intraxonal proteins can all be labeled, and their kinetics followed in vivo without killing the animal. When the nerve is removed at the conclusion of this study, tissue autoradiography and biochemical studies can be performed. The initial studies will validate the labeling method and establish normative kinetic and biochemical data. This approach will then be applied to animal models of peripheral neuropathy and to hereditary canine spinal muscular atrophy, a model of motor neuron disease. In addition, the method will be extended to allow labeling and measuring of fast anterograde and retrograde transport in biopsied peripheral nerve. These studies are intended to provide a technique for studying axonal transport in human nerve biopsies.